1. Field of the Invention
This invention relates to condensed benzene derivatives, a medicine for treating or preventing cerebral circulation disorder, cerebral metabolism disorder, and memory disturbance comprising the same, and intermediates for preparing the same.
2. Description of the Background Art
Senile dementia caused by such cerebral disorders as cerebrovascular disorder, cerebral circulation disorder, cerebral metabolism disorder, and memory disturbance has become a social problem in the society with prolonged lifespan. Development of medicines useful for treating or preventing these diseases are thus desired.
A recent clinical report [M. F. Mazurek et al., Neurology, 36, 1133 (1986)] revealed a remarkable decrease of peptides participating in memory or neurotransmission in brains of senile dementia patients.
Prolyl endopeptidase inhibitors are known as exhibiting anti-amnesic activity, since prolyl endopeptidase hydrolyzes and inactivates neuropeptides including proline in brains such as vasopressin [European Patent Publication No. 232849, Folia Pharmacologica Japonica, 89, 323 (1987), and id., 89, 243 (1987)].
Drugs improving cerebral circulation, cerebral vasodilators, cerebral metabolism accelerators, and the like are clinically used as medicines for treating cerebrovascular disorders. These medicines, however, exhibit only insufficient improvement in neurological symptoms or inability of daily life in the patients, even though they are recognized to improve subjective symptoms. Therefore, development of a medicine possessing both cerebral metabolism improving effects and anti-amnesic effects based on prolyl endopeptidase inhibitory activity has been desired.
The present inventors have undertaken extensive studies on various compounds in order to obtain a novel medicine for treating or preventing cerebral circulation disorder, cerebral metabolism disorder, and memory disturbance. As a result, the present inventors found that a condensed benzene derivative represented by the following formula (I) exhibited both prolyl endopeptidase inhibitory activity, anti-hypoxic activity and anti-amnesic and cerebral circulation/metabolism improving activity at the same time. Such a finding has led to the completion of the present invention.